Project 4 Project Summary Project 4 will leverage the increasing popularity of smartphones to improve upon standard in-clinic cognitive testing, providing a robust characterization of cognition in participants enrolled in the Healthy Aging and Senile Dementia PPG. One of the most important and face-valid indicators of Alzheimer disease (AD) is a change in cognition, but assessing cognition in-clinic has several drawbacks. First, performance is influenced by day-to- day fluctuations in stress, fatigue, sleep patterns, and mood. Second, the testing takes place in environments that are fundamentally different from where cognitively demanding tasks are performed in daily life. Finally, by design, cognition is typically assessed very infrequently, usually once per year (as currently is the case in HASD). One solution would be to increase the frequency of in-clinic testing or to complete assessments in the natural environments in which participants use cognition such as their homes, workplaces, while traveling, etc., but this is impractical and burdensome, especially for older adults. Project 4 will provide a solution to these difficulties by taking advantage of the increasing popularity of smartphones. Smartphone usage is climbing in every age category, and even in older adults, 50% have and regularly use internet-enabled smartphones. In Project 4, we have designed an iOS and Android app called the Ambulatory Research in Cognition (ARC) app that will be installed on HASD participants' personal smartphones. If participants do not own a smartphone or have an antiquated model, we will provide a study phone for use while enrolled. Every six months, participants will complete extremely brief (<3 minutes each) testing sessions 4x/day over the course of one week. Tests are averaged across the week to provide a score that captures and normalizes natural variability and dramatically increases reliability. Pilot studies show that ARC assessments demonstrate extraordinary reliability, ranging from 0.92 to 0.99. Another advantage is the ability to measure variability within a day, across a week, and across the 6-month intervals of assessments. We hypothesize that ARC assessments will be more sensitive than in-clinic assessments to disease stage and AD biomarkers and that amyloid-positive HASD participants will show more variability in cognitive performance than amyloid-negative participants, even in the preclinical stages of disease. If successful, the increases in sensitivity and reliability of ARC assessments will provide extraordinary statistical power to characterize cognitive decline in observational studies of AD. In addition, ARC assessments could benefit clinical trials by shortening trial duration and requiring fewer participants.